Determination of CRIM Status and Longitudinal Follow-up of Individuals With Pompe Disease

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This is a longitudinal natural history study of Infantile Pompe disease. The investigators will regularly collect and review medical information for up to 10 years regarding the diagnosis of Pompe disease, response to enzyme replacement (ERT) using alglucosidase alfa (Myozyme) and response to immunosuppressive therapy in cases at risk for developing or those who have developed high and sustained antibodies to ERT. A subset of de-identified information about the natural history of Pompe disease and the response to treatment will be incorporated into the Lysosomal Disease Network (LDN) disease registry. The LDN is a nonprofit organization of scientists located around the world whose research focuses on Lysosomal disease.

The specific aims of this study are:

To determine and correlate Cross-Reactive Immunological Material (CRIM) status with the GAA gene mutations found on these patients

To validate an approach for determining CRIM status from whole blood sample, with the gold standard determination of CRIM status by skin fibroblasts and mutation analysis

To explore the clinical treatment response and natural history of CRIM-positive and CRIM-negative Pompe disease patients with and without immune modulation

To investigate the role of immune response to treatment

Condition or disease

Intervention/treatment

Pompe Disease

Other: Observational

Detailed Description:

Infantile-onset Pompe disease is an inherited disorder caused by lack of or defect in the enzyme acid alpha-glucosidase (GAA). GAA enzyme deficiency causes glycogen to build up and damage cells throughout the body, especially in the heart and muscles, which is normally diagnosed within the first months of life. Current treatment for Pompe disease involves enzyme replacement therapy (ERT) using the drug alglucosidase alfa (Myozyme), which provides a form of the GAA enzyme to replace the enzyme that is missing or not working properly in the patient's blood.

In this study, the investigators will learn about the patient's ability to tolerate ERT. Cross-Reactive Immunological Material (CRIM) is a measurement of natural GAA production and an important factor that affects how patients respond to ERT with Myozyme. Children who produce some natural GAA are classified as CRIM positive (+), while children who do not produce any natural GAA are classified as CRIM negative (-). Children who are CRIM+ generally tolerate ERT well. But, children who are CRIM-, and some children classified as CRIM+, have a poor response to ERT due to complications from an immune response against the drug. Treatments are currently being developed to stop this immune response and prevent complications from ERT.

This is a longitudinal natural history study of Infantile Pompe disease. The investigators will regularly collect and review medical information for up to 10 years regarding the diagnosis of Pompe disease, response to enzyme replacement (ERT) using alglucosidase alfa (Myozyme) and response to immunosuppressive therapy in cases at risk for developing or those who have developed high and sustained antibodies to ERT. A subset of de-identified information about the natural history of Pompe disease and the response to treatment will be incorporated into the Lysosomal Disease Network (LDN) disease registry. The LDN is a nonprofit organization of scientists located around the world whose research focuses on Lysosomal disease.

The specific aims of this study are:

To determine and correlate Cross-Reactive Immunological Material (CRIM) status with the GAA gene mutations found on these patients

To validate an approach for determining CRIM status from whole blood sample, with the gold standard determination of CRIM status by skin fibroblasts and mutation analysis

To explore the clinical treatment response and natural history of CRIM-positive and CRIM-negative Pompe disease patients with and without immune modulation

Clinical response to enzyme replacement therapy (ERT) using alglucosidase alfa (Myozyme) [ Time Frame: Up to 10 years ]

Medical records will be tracked for up to 10 years to follow clinical response to ERT. This will allow us to gain an understanding of CRIM status in relation to clinical outcome and development for these subjects.

Secondary Outcome Measures
:

Response to Immune Tolerance Induction (ITI) [ Time Frame: Up to 10 years ]

Medical records will be tracked for up to 10 years to follow clinical response to Immune Tolerance Induction (ITI) for patients who are CRIM- or CRIM+ with high antibody titers. This will allow us to increase our understanding of the history of Pompe disease in relation to treatment interventions and the role of high antibody titers in terms of patient outcome in order to develop strategies to ameliorate the immune response and other factors that may affect response to ERT.

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Ages Eligible for Study:

up to 18 Years (Child, Adult)

Sexes Eligible for Study:

All

Accepts Healthy Volunteers:

No

Sampling Method:

Non-Probability Sample

Study Population

Study subjects will be babies/children with a confirmed diagnosis of infantile-onset Pompe disease who are:

seen by the clinical staff of Duke Division of Medical Genetics, or

whose physician or parent contacts the Duke Division of Medical Genetics with the wish to participate in this CRIM research study.